1 / 21

Lead Site: Stanford University - Carol Conrad, MD and Rabin Tirouvanziam, PhD

A Multi-Center, Phase IIb , Randomized, Placebo-Controlled, Double-Blind Study Of The Effects Of N- Acetylcysteine (NAC) On Redox Changes And Lung Inflammation In Cystic Fibrosis Patients. Lead Site: Stanford University - Carol Conrad, MD and Rabin Tirouvanziam, PhD.

matia
Télécharger la présentation

Lead Site: Stanford University - Carol Conrad, MD and Rabin Tirouvanziam, PhD

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. A Multi-Center, Phase IIb, Randomized, Placebo-Controlled, Double-Blind Study Of The Effects Of N-Acetylcysteine (NAC) On Redox Changes And Lung Inflammation In Cystic Fibrosis Patients. Lead Site: Stanford University - Carol Conrad, MD and Rabin Tirouvanziam, PhD

  2. Participating sites:University of Utah – Barbara Chatfield, MDBirmingham Children’s Hospital – J.P. Clancy, MDYale University – Marie Egan, MDDuke University – Peter Michelson, MDNational Jewish Hospital – David Nichols, MDColumbia University – Lynne Quittel, MDChildren’s Hospital of Philadelphia – Ron Rubenstein, MDChildren’s Hospital of Pittsburgh – Jonathan Spahr, MDPenn State, Hershey – Robert Vender, MDUniversity of Florida, Gainesville – Veena Antony, MD

  3. Effects of NAC on Redox Changes and Lung Inflammation • Hypothesis: GSH replenishment to blood neutrophils will allow for a decrease neutrophil inflammation in the sputum of CF subjects as determined by sputum elastase activity. • Oral NAC fizzy tablets, 900 mg PO TID, or placebo • Primary efficacy measures: sputum elastase activity (ELISA) • Secondary efficacy measures: FEV1 (% pred.) • Sputum, blood, PFT’s, and QOL on Day 0 and Week 6, Week 12, and Week 24.

  4. Phase IIB Proof of Concept • Staged enrollment, Stanford first cohort • In-depth studies to assess if any potential for pulmonary hypertension • 16 subjects completed study • No AE’s related to NAC • No PH (detected by ECHO, DLCO, no free NAC in plasma, no S-nitrosylated NAC detected in plasma) • Other sites initiated in November 2009 • 11 sites/80 subjects planned/ 70 enrolled • Smaller panel PH studies

  5. Secondary Objectives • Eval effect of NAC on number of pulmonary and sinus exacerbations, antibiotic use • Eval effect of NAC on inflammation in the lungs (neutrophil count) • Eval effect of NAC on pulmonary function • Eval effect of NAC on weight • Eval effect of NAC on QOL

  6. Safety Objectives • Safety and tolerability • Eval if NAC causes pulmonary hypertension if used chronically in high doses

  7. Inclusion Criteria • 7 years of age and older • Able to tolerate sputum induction • Perform reproducible spirometry • Stable mild to moderate lung disease • No use of acute antibiotics in prev. 4 weeks • Must stop use of anti-oxidants in any form at least 6 weeks prior to and for the duration of the study • Usual doses of Vit E and C are allowed

  8. Exclusion Criteria • NSAID use in previous 1 week • To assure sputum neutrophil count and elastase are at ‘baseline’ • Initiation of chronic dosing with azithro, ibuprofen, TOBI, IH Aztreonam or Colistin within previous 6 weeks • Liver disease • Active ABPA in previous 6 months • Acetaminophen use in previous 3 days

  9. SAFETY/EFFICACY EFFICACY 91 Participants Assessed for Eligibility 16 Randomized To Stanford Cohort • 6 Not Eligible • 2 unable to forego Vit E, Vit C or more than 2 alcoholic drinks per day • 16 Failed screening • FEV1 > 85% predicted Staggered Enrollment: To Assess Potential Development of PH, enrollment began at Stanford. Interim safety analysis by DSMB review of PH data after 8 subjects had completed Week 8 visit. Other sites began enrollment. 70 Randomized 34 Assigned to Placebo 36 Assigned to NAC 8 Assigned to NAC 8 Assigned to Placebo Follow up at: Week 12: 33 Week 24: 30 Follow up at: Week 12: 32 Week 24: 32 Follow up at: Week 12: 16 Week 24: 16 6 Withdrawals 5 Subject Decision 1 Due to AE not drug related 2 Withdrawals 2 Subject Decision 0 withdrawals ITT Population: 36 NAC 34 Placebo PP Population: 18 NAC 23 Placebo

  10. Baseline Characteristics

  11. Baseline Characteristics – Pulmonary Function

  12. Summary - Primary and Secondary Analyses

  13. NeutrophilElastase (Log10) DLog10HNE (mL/mL)

  14. Exacerbations and Related Events

  15. Time to Pulmonary Exacerbation

  16. Adverse Events

  17. Change in FEV1 (Absolute volume) Relative % DFEV1 (L)

  18. CFRSD Number of Respiratory Symptoms

  19. CFQ-R Respiratory Score

  20. Acknowledgments

  21. Thank-You To All Study Participants!!! Discoveries and advances can’t be made without your participation. You are the best!

More Related